The clinical course of herpes zoster: a prospective study in primary care

Authors: Helgason S, Sigurdsson J, Gudmundsson S.
Source: European Journal of General Practice. 2:12-16.
March, 1996.
Institution: National University Hospital, Iceland.
Financial support: Icelandic Council of Science, Icelandic College
of Family Physicians, Research Fund of the University of Iceland.

This paper was brought to my attention by one of its authors (Dr. Sigurdur
Helgason). It is a nice illustration of an approach that is sure to become
more widespread: the statistical analysis of data obtained via computerized
medical records from a primary care setting.

Summary

Background

This study from Iceland was designed to obtain an accurate assessment
of the incidence and course of herpes zoster in the primary care setting,
making use of the increasing availability of computerized medical record
systems in ambulatory practice.

Methods

Recruitment of subjects: Recruitment was organized around GP physicians.
GP's were asked to participate if they had a computerized medical record
system and agreed to the protocol. A total of 62 GP's participated, caring
for about 1/3 of the population of Iceland. They were asked to report all
new cases of acute Zoster in their practice, between January, 1990 and
June, 1995. The diagnosis of Zoster was on clinical criteria alone; patients
gave verbal consent to participate and were excluded if there was cognitive
impairment precluding an accurate history.

Data collected: Upon notification of a case, one of the authors
of the study contacted the patient and ascertained data about the rash,
associated symptoms, treatment and other medical conditions. Patients were
followed-up by telephone at least 1, 3 and 12 months after initial appearance
of the rash and more frequently if there was postherpetic neuralgia.

Results

Patients recruited: 457 patients were included in the study, after
exclusion of 48 patients (38 for incorrect diagnosis as judged by the authors).
Most patients were reported by the GP's participating in the study (75%),
but 25% were recruited by reviewing computer printouts of medical records.
The number of person-years observed was 229,547.

Incidence of zoster: Overall 2.0 per 1000 person years. Age-standardized
in the over 60 population: males 3.6 and females 5.6 per 1000 years. Overall
distribution (not age-standardized) bimodal, with one quarter of the cases
in the population under 20 years of age and 34% in the 60 and over population.

Recurrent zoster: One percent during the study period, 5% including
prior history.

Associated conditions: Diabetes in 13 patients (2%), malignancies
within 6 months of zoster in 5 patients (1%), HIV in one and steroid or
cyclosporine therapy in 5 (1%).

Postherpetic neuralgia:

At one month after onset (information was available for 370 of 462 episodes):

Age under 40: 98% were pain free, 2% had mild pain.

Age 40-60: 79% were pain free, 21% had mild/moderate pain.

Age over 60: 59% were pain free, 37% had mild/moderate pain, 3% had severe
pain

At three months after onset (information available for 427 of 462 episodes):

Age under 40: 99.5% were pain free, 0.5% had mild pain.

Age 40-60: 95% were pain free, 5% had mild pain.

Age over 60: 81% were pain free, 18% had mild/moderate pain, 1% had severe
pain

At twelve months after onset (information available for 457 of 462 episodes):

Age under 40: 100% were pain free.

Age 40-60: 98% were pain free, 2% had mild pain.

Age over 60: 92% were pain free, 8% had mild/moderate pain.

Severity / complications / treatment: Ophthalmic zoster developed
in 39 patients, 14 had ocular involvement. Eighteen patients were hospitalized
for zoster (4%). Only 17 patients (4%) were treated with systemic acyclovir,
mainly because of age and severity of rash.

Authors' Discussion

The authors compare their results to those of other studies, which have
shown largely comparable findings. They note that their incidence of zoster
in the younger population is higher than previously noted and that their
incidence of post-herpetic neuralgia is similar to earlier studies but
lower than that found in the placebo arm of recent trials of acyclovir.
They estimate that a GP caring for 2000 patients can expect to see zoster
four times a year and post-herpetic neuralgia lasting more than three months
every other year, principally in the older population. Finally, in their
series zoster was rarely associated with major illnesses.

Comment

This well-designed study provides detailed epidemiologic data about the
incidence and course of herpes zoster, largely untreated with antivirals,
in an outpatient, primary care setting. From a methodological standpoint,
I have three caveats/questions. The authors present the sex and age distribution
of patients with zoster in a graph, but this is not adjusted for the age
distribution in the population studied and thus cannot be extrapolated
to populations with different age distributions. Second, the authors do
not specify exactly how the number of person years observed was obtained,
which is central to the calculation of incidence. Was the number of person
years observed calculated using patients actually in the medical records
of the participating GP's, or was it based on patients in the geographic
catchment area of these physicians? If the former, and if a significant
number of people in the GP's catchment area were not in that physician's
computerized records, the population at risk would have been underestimated
and the incidence would have been overestimated. Finally, six-months follow-up
time may be a bit short to conclude about the prevalence of malignancy
in patients with zoster.

Beyond the data presented here, the concept of using outpatient computerized
medical records to obtain data for such a study is an important one and
raises a number of interesting issues:

Electronic medical record systems offer the potential to obtain reams of
incidence data with relative ease. For this data to be accurate, however,
the population being observed or the population at risk needs to be clearly
defined. Since, in many countries, patients shift between health care providers,
it is necessary to have a unique patient identifier that is used when analyzing
such data. As noted earlier, if a large number of patients are potential
clients of a physician but not in that physician's EMR system, the population
at risk will be under-estimated and incidences over-estimated.

If computerized medical record systems contain data about patients that
is coded differently or is in other ways not adequately standardized, it
will be difficult to pool information. When pooling data from different
record systems, we will, in general, be limited to making statements about
data that is present in all of them. We are, in a sense, limited to the
lowest common denominator when pooling such data. Some sort of standardization,
a minimal data-set, is urgently needed.

As a corollary to the above, a "Rosetta Stone" or meta-medical record which
would allow mapping of the main components of every type of EMR to a standard
record would be very useful and would permit cross-platform analysis of
data from multiple systems. Each vendor of an EMR system would then be
responsible for providing a mapping of its data to the standardized meta-medical
record. This would also allow easy portability of a patient's computerized
chart from one system to another.

Enabling private practitioners to provide data for studies such as this
one has significant benefits. It allows health care researchers to conduct
studies in the "real world" with greater ease, while it also allows practitioners
in the trenches of primary care to participate in research in a meaningful
way. This could be an invigorating and gratifying experience for both sides.

On a more cautionary note, the number of studies that can and will be performed
using this approach is practically limitless. Once a mechanism is in place
for accessing and exploiting the data present in private practitioners'
offices, that data can be "massaged" ad infinitum. Those with a particular
axe to grind or potion to sell will be able to sit at their computers and
come up with statistics to back them up. If the calcium channel blocker
industry gets annoyed at bad publicity, it can run "ACE inhibitor prescriptions"
against every disease in the ICD-9 book until a correlation pops up that
can then be "investigated" and publicized. Just as post-hoc subgroup analysis
is subject to skepticism, we will, in the long run, need criteria for the
evaluation of statistically derived outpatient data.

5/9/96

Reader comments

First: I want to emphasize that the main reason and actually the only
reason for this study was to find the point prevalence (traditionally called
incidence in zoster studies of this kind) of postherpetic neuralgia at
different time points after acute zoster in a primary care population.
We have an age breakdown of 90% of the persons under observation, or a
third of Icelanders. That is, nearly all practices could give the age distribution
of the patients they cared for (registered). After comparing this with
the age distribution of the total population (just over 261 thousand in
1992) we found it to be almost the same. We extrapolated from the 90% available,
assuming the practices providing age strata were similar to those not providing
this information.

Secondly: The number of person years was determined by multiplying the
number of patients registered with each practice or GP by the duration
of time each particular practice or GP participated in the study. Bias
in estimating incidence due to a possible difference between catchment
area/population and the population actually registered ("belonging") to
a particular GP is not likely. The reason is that to be included as a case
of zoster the patient had to be registered with a participating GP. All
patients diagnosed with zoster but whose GP was not in the study were excluded,
even if a GP in the study diagnosed them (during call or other services).
This ment that GP´s not in the study, but who knew of it, often contacted
me telling me about new cases in their care which I had to refuse, of course.
One more point is that we kept a low profile with this study because we
wanted only patients who normally would have sought medical attention for
their zoster (avoiding publicity/referral bias).

Thirdly: I agree that 6 months is hardly enough follow up with malignancy
in mind. What we did was to follow all for 12 months. I am a little obsessive
when it comes to follow-up and those moving abroad were almost all eventually
reached via phone. 99% follow-up over a year must be a record. The time
frame of 6 months prior to or after the zoster episode was a collective
decision. Actually, looking back at the data and extending this to 12 months
after the zoster would not have changed the actual number of patients with
malignancy "associated" with zoster.

Finally: Of the 14 patients still having pain after 12 months I have
contacted eleven, 24 to 52 months after the zoster episode. One of the
two patients with moderate pain was unchanged, but the other one defined
his pain as mild and improving. Of the 12 patients with mild pain, two
were worse, three better (pain free), four unchanged and three have not
been reached/evaluated.

Sincerely,
Sigurður Helgason

That pretty much clarifies all the questions I had. Thanks for taking
the time to answer in so much detail. -- mj

In your study did you find any incidence of Herpes Zoster during pregnancy?
If so, how was it treated?
Did Herpes Zoster and/or its treatment lead to any birth defects?

Sincerely,

Manish H. Shah.

Dr. Sigurdur Helgason, study author, responds:

Date: Thu, 8 Jan 1998
From: Sigurdur Helgason <sh@centrum.is>

My short answer without going to the original data is:

Six women were known to be pregnant. None were treated and in no case
were there any complications - maternal or foetal. At follow up (patient
contact 12 months after the zoster and GP contact about 24 months after
the zoster) there was no indication of complications. Although we should
keep in mind that we did not examine babies or ask focused questions in
that direction as it is our experience that zoster in pregnancy is a benign
condition.

Sincerely yours Sigurður Helgason.

Date: Fri, 18 Sep 1998
From: BUNY2love@aol.com

I read with interest your perspective on clinical data bases in physician
offices. Conceptually this is where we all should be heading; however
the US is still struggling with continuity of disease classifications at
the hospital level. So much of the classification process is geared
toward reimbursement issues instead of clinical pertinence. While
it seems insurmountable to standardize coding, it's what is needed to control
costs and improve patient care.

Note

This website is not intended to provide medical advice. It
is a forum where health care professionals can discuss articles from the
recent medical literature. Articles in medical journals often present information
which is incomplete, preliminary or hypothetical. I cannot assume responsibility
for the accuracy of the articles summarized, nor for the accuracy of any
reader comments. The summaries, my comments and reader comments should
not be used in lieu of medical advice, which should always be sought from
an appropriate health care provider.